This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adolescent hyperandrogenemia appears to be a precursor to adult polycystic ovary syndrome (PCOS). Adult women with PCOS have reduced sensitivity to progesterone inhibition of GnRH pulsatility. Androgens appear to play a role in mediating progesterone sensitivity, as sensitivity can be restored with the use of the androgen blocker flutamide. We have found that some hyperandrogenemic adolescent girls show reduced sensitivity to progesterone inhibition of GnRH pulsatility while others maintain sensitivity despite equivalent androgen levels. All of the hyperandrogenemic girls who maintained progesterone sensitivity were Hispanic, suggesting a possible genetic etiology. Androgen receptor CAG repeat length polymorphisms confer variable androgen receptor transactivation activities. The distribution of androgen receptor CAG repeat length polymorphism varies in different racial and ethnic groups. We propose to examine the androgen receptor CAG repeat length in hyperandrogenemic adolescent girls with and without sensitivity to progesterone inhibition of GnRH pulsatility. The results will allow us to determine whether androgen receptor CAG repeat polymorphisms play a role in determining susceptibility to the neuroendocrine effects of hyperandrogenemia.